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PloS One 2019Cachexia occurs in individuals affected by chronic diseases in which systemic inflammation leads to fatigue, debilitation, decreased physical activity and sarcopenia....
BACKGROUND
Cachexia occurs in individuals affected by chronic diseases in which systemic inflammation leads to fatigue, debilitation, decreased physical activity and sarcopenia. The pathogenesis of cachexia-associated sarcopenia is not fully understood.
OBJECTIVES
The aim of this systematic review is to summarize the current evidence on genes expressed in the skeletal muscles of humans with chronic disease-associated cachexia and/or sarcopenia (cases) compared to controls and to assess the strength of such evidence.
METHODS
We searched PubMed, EMBASE and CINAHL using three concepts: cachexia/sarcopenia and associated symptoms, gene expression, and skeletal muscle.
RESULTS
Eighteen genes were studied in at least three research articles, for a total of 27 articles analyzed in this review. Participants were approximately 60 years of age and majority male; sample size was highly variable. Use of comparison groups, matching criteria, muscle biopsy location, and definitions of cachexia and sarcopenia were not homogenous. None of the studies fulfilled all four criteria used to assess the quality of molecular analysis, with only one study powered on the outcome of gene expression. FOXO1 was the only gene significantly increased in cases versus healthy controls. No study found a significant decrease in expression of genes involved in autophagy, apoptosis or inflammation in cases versus controls. Inconsistent or non-significant findings were reported for genes involved in protein degradation, muscle differentiation/growth, insulin/insulin growth factor-1 or mitochondrial transcription.
CONCLUSION
Currently available evidence on gene expression in the skeletal muscles of humans with chronic disease-associated cachexia and/or sarcopenia is not powered appropriately and is not homogenous; therefore, it is difficult to compare results across studies and diseases.
Topics: Cachexia; Female; Gene Expression; Humans; Male; Middle Aged; Muscle, Skeletal; Sarcopenia
PubMed: 31498843
DOI: 10.1371/journal.pone.0222345 -
Journal of Neurotrauma Apr 2021There is a growing literature on the impact of genetic variation on outcome in traumatic brain injury (TBI). Whereas a substantial proportion of these publications have...
There is a growing literature on the impact of genetic variation on outcome in traumatic brain injury (TBI). Whereas a substantial proportion of these publications have focused on the apolipoprotein E (APOE) gene, several have explored the influence of other polymorphisms. We undertook a systematic review of the impact of single-nucleotide polymorphisms (SNPs) in non-apolipoprotein E (non-APOE) genes associated with patient outcomes in adult TBI). We searched EMBASE, MEDLINE, CINAHL, and gray literature from inception to the beginning of August 2017 for studies of genetic variance in relation to patient outcomes in adult TBI. Sixty-eight articles were deemed eligible for inclusion into the systematic review. The SNPs described were in the following categories: neurotransmitter (NT) in 23, cytokine in nine, brain-derived neurotrophic factor (BDNF) in 12, mitochondrial genes in three, and miscellaneous SNPs in 21. All studies were based on small patient cohorts and suffered from potential bias. A range of SNPs associated with genes coding for monoamine NTs, BDNF, cytokines, and mitochondrial proteins have been reported to be associated with variation in global, neuropsychiatric, and behavioral outcomes. An analysis of the tissue, cellular, and subcellular location of the genes that harbored the SNPs studied showed that they could be clustered into blood-brain barrier associated, neuroprotective/regulatory, and neuropsychiatric/degenerative groups. Several small studies report that various NT, cytokine, and BDNF-related SNPs are associated with variations in global outcome at 6-12 months post-TBI. The association of these SNPs with neuropsychiatric and behavioral outcomes is less clear. A definitive assessment of role and effect size of genetic variation in these genes on outcome remains uncertain, but could be clarified by an adequately powered genome-wide association study with appropriate recording of outcomes.
Topics: Apolipoproteins E; Brain Injuries, Traumatic; Brain-Derived Neurotrophic Factor; Cytokines; Genetic Association Studies; Genome-Wide Association Study; Humans; Polymorphism, Single Nucleotide; Treatment Outcome
PubMed: 29799308
DOI: 10.1089/neu.2017.5583